The impact of the association between Val16Ala-SOD2 SNP and SOD2 immunohistochemistry expression in the prognosis of patients with esophageal cancer.

INTRODUCTION: Esophageal cancer is an extensive public health issue worldwide, warranting the search for biomarkers related to its risk and progression. Previous studies have indicated an association between Val16AlaSOD2 single nucleotide polymorphism in the gene encoding the enzyme superoxide dismutase 2 and esophageal cancer. However, further investigations are needed to clarify its role in disease risk and progression. OBJECTIVE: To investigate the role of Val16AlaSOD2-SNP in esophageal cancer progression and in the survival of patients METHODS: Tumor samples were utilized for Val16Ala-SNP genotyping, while SOD2 expression levels in tissue were assessed using immunohistochemistry. A SOD2 Val16Ala-SNP database was used to obtain information on the genotype of healthy individuals. Risk and overall survival analyzes were performed. RESULTS: The Val16Ala SNP was associated with an increased risk of esophageal cancer (RR 2.18, 95%CI 1.23-3.86), regardless of age and gender, but did not have a significant effect on patient survival. In contrast, weak SOD2 expression demonstrated a significantly associated with poor overall survival after treatment, independent of other clinicopathological variables (HR, 0.41; 95% CI, 0.22-0.79 P = 0.007). CONCLUSIONS: Val16Ala SNP was positively associated with esophageal cancer, and the expression of SOD2 was an independent prognostic marker.

Mechanisms involved in anti-aging effects of guarana (Paullinia cupana) in Caenorhabditis elegans.

Guarana (Paullinia cupana) is habitually ingested by people in the Amazon region and is a key ingredient in various energy drinks consumed worldwide. Extension in longevity and low prevalence of chronic age-related diseases have been associated to habitual intake of guarana. Anti-aging potential of guarana was also demonstrated in Caenorhabditis elegans; however, the mechanisms involved in its effects are not clear. Herein, we investigated the putative pathways that regulate the effects of guarana ethanolic extract (GEE) on lifespan using C. elegans. The major known longevity pathways were analyzed through mutant worms and RT-qPCR assay (DAF-2, DAF-16, SKN-1, SIR-2.1, HSF-1). The possible involvement of purinergic signaling was also investigated. This study demonstrated that GEE acts through antioxidant activity, DAF-16, HSF-1, and SKN-1 pathways, and human adenosine receptor ortholog (ADOR-1) to extend lifespan. GEE also downregulated skn-1, daf-16, sir-2.1 and hsp-16.2 in 9-day-old C. elegans, which might reflect less need to activate these protective genes due to direct antioxidant effects. Our results contribute to the comprehension of guarana effects in vivo, which might be helpful to prevent or treat aging-associated disorders, and also suggest purinergic signaling as a plausible therapeutic target for longevity studies.

Neuroprotective Effects of Guarana (Paullinia cupana Mart.) against Vincristine in Vitro Exposure.

BACKGROUND: Vincristine (VCR) is not a specific chemotherapeutic drug, responsible for cause several side effects. In this sense, many natural products have been studied to reduce this problem. Objetives: To examine the guarana neuroprotective effect in mice brain and cerebellum cells against vincristine (VCR) exposition. DESIGN: An in vitro study was performed using mice brain and cerebellum mice in monolayer culture. First, cells were exposed to VCR (0.009 µM for 24 hours and 0.0007 µM for 72 hours) to measure the cytotoxicity effect. Also, the cellular effect of hydroalcoholic extract of guarana (10; 30; 100 and 300 µg/mL) was evaluated in the same cells in 24 and 72 hours. After that, cells were exposed to VCR and guarana extract to evaluate the neuroprotective effect of guarana. MEASUREMENTS: Cell viability was analyzed by MTT, Free dsDNA and LHD Assays. Moreover, metabolism oxidative profile was evaluated by reactive oxygen species (ROS), lipoperoxidation (LPO) and catalase (CAT) levels through DCFH-DA, TBARS and Catalase Activity Assays, respectively. RESULTS: Our findings revealed that VCR caused neuronal cytotoxicity by reducing cell viability and increasing ROS and LPO levels. On the other hand, guarana did not cause cell damage in none of tested concentrations. In addition, guarana exhibited a notable protective effect on brain and cerebellum cells exposed to VCR by increasing cell viability, stimulating CAT activity, reducing levels of ROS and LPO. CONCLUSIONS: In this sense, guaraná is a remarkable antioxidant fruit that could be a target in new therapies development to reduce VCR neurotoxicity. .

Mechanisms involved in anti-aging effects of guarana (Paullinia cupana) in Caenorhabditis elegans

Guarana (Paullinia cupana) is habitually ingested by people in the Amazon region and is a key ingredient in various energy drinks consumed worldwide. Extension in longevity and low prevalence of chronic age-related diseases have been associated to habitual intake of guarana. Anti-aging potential of guarana was also demonstrated in Caenorhabditis elegans; however, the mechanisms involved in its effects are not clear. Herein, we investigated the putative pathways that regulate the effects of guarana ethanolic extract (GEE) on lifespan using C. elegans. The major known longevity pathways were analyzed through mutant worms and RT-qPCR assay (DAF-2, DAF-16, SKN-1, SIR-2.1, HSF-1). The possible involvement of purinergic signaling was also investigated. This study demonstrated that GEE acts through antioxidant activity, DAF-16, HSF-1, and SKN-1 pathways, and human adenosine receptor ortholog (ADOR-1) to extend lifespan. GEE also downregulated skn-1, daf-16, sir-2.1 and hsp-16.2 in 9-day-old C. elegans, which might reflect less need to activate these protective genes due to direct antioxidant effects. Our results contribute to the comprehension of guarana effects in vivo, which might be helpful to prevent or treat aging-associated disorders, and also suggest purinergic signaling as a plausible therapeutic target for longevity studies.

Impact of the Ile105Val Polymorphism of the Glutathione S-transferase P1 (GSTP1) Gene on Obesity and Markers of Cardiometabolic Risk in Young Adult Population.

The aim of the study was to investigate the association between Glutathione S-transferase P1 (GSTP1) gene polymorphism with obesity and markers of cardiometabolic risk. A cross-sectional study was carried out in individuals aged≥18 and ≤30 years. The study included 54 normal weight, 27 overweight and 68 obese volunteers. Anthropometric measurements and biochemical parameters were evaluated, the DNA was extracted from blood samples and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure GSTP1 Ile105Val gene polymorphism of the study participants. Also, biochemical analysis and hormone assays were carried out. A positive association between GSTP1 polymorphism and obesity was observed on subjects carrying at least one G allele (AG and GG). GG genotype was found only in the obese group. The G allele carriers presented 2.4 times higher chance of obesity when compared to those with the AA genotype. These results were independent of sex and age. We suggest that despite a study in population regional (south of Brazil), the GSTP1 gene polymorphism may play a significant role in the increase of susceptibility of obesity and contribute to identify the cardiovascular risk in young adults.

Seminal cell-free DNA levels measured by PicoGreen fluorochrome are associated with sperm fertility criteria.

Previous investigations suggested that elevated cell-free DNA (cfDNA) can indicate non-healthy states. However, the potential association between cfDNA seminal plasma levels and fertility sperm parameters has not yet been determined. Therefore, the present study evaluated the association between seminal cfDNA levels and sperm fertility criteria to determine the use of seminal cfDNA quantification. An in vivo protocol quantified cfDNA levels of semen samples obtained from 163 male patients using fluorescent PicoGreen dye staining. To confirm if semen cfDNA quantification is realistic, an in vitro complementary test was performed using three or four semen samples. The fresh sperm samples were exposed to paraquat that generates high levels of superoxide anion causing oxidative stress and cell mortality. The results showed significant association between dsDNA levels and several sperm fertility parameters, such as low viability and alterations of motility and morphology. The in vitro analysis confirmed the association between dsDNA levels and sperm viability. Together, these results suggest that dsDNA levels could be an important biomarker to test sperm fertility.

The effects of rosuvastatin on lipid-lowering, inflammatory, antioxidant and fibrinolytics blood biomarkers are influenced by Val16Ala superoxide dismutase manganese-dependent gene polymorphism.

Rosuvastatin is a cholesterol-lowering drug that also attenuates the inflammatory process and oxidative stress via the reduction of superoxide anion production. Superoxide anions are metabolized by manganese-dependent superoxide dismutase (MnSOD or SOD2) in the mitochondria. In humans, there is a gene polymorphism where a change of alanine (Ala) to valine (Val) occurs at the 16th amino acid (Ala16Val-SOD2). The VV genotype has been associated with the risk of developing several metabolic diseases, such as hypercholesterolemia. Thus, to further explore this phenomenon, this study investigated the influence of the Val16Ala-SOD2 polymorphism on the lipid profile and inflammatory and fibrinolytic biomarkers of 122 hypercholesterolemic patients undergoing the first pharmacological cholesterol-lowering therapy who were treated with 20 mg rosuvastatin for 120 days. The findings indicate that the VV patients who present a low-efficiency SOD2 enzyme exhibit an attenuated response to rosuvastatin compared with the A-allele patients. The effect of rosuvastatin on inflammatory and fibrinolytic biomarkers was also less intense in the VV patients. These results suggest some pharmacogenetic effects of Val16Ala-SOD2 in hypercholesterolemia treatment.

Toxicity of irrigating solutions and pharmacological associations used in pulpectomy of primary teeth.

AIM: To evaluate the in vitro toxicity of irrigating solutions and pharmacological associations used in the pulpectomy of primary teeth. METHODOLOGY: The cell viability (MTT), lipid peroxidation (TBARS), alkaline comet assay and GEMO tests were performed to evaluate the cytotoxicity and genotoxicity of solutions: sodium hypochlorite (1% and 2.5%), 2% chlorhexidine, 6% citric acid and 17% EDTA, which were tested, individually and in association, exposing human peripheral blood mononuclear cells (MTT, TBARS and alkaline comet assay), at 24 and 72 h, and dsDNA (GEMO). After performing the Kolmogorov-Smirnov test, data were analysed by anova followed by Dunnett's post hoc test, and Kruskal-Wallis followed by Dunn post hoc test. A significance level was established at P < 0.05. RESULTS: All irrigating solutions and pharmacological associations reduced cell viability at 24 h (P < 0.05). These reductions were maintained after 72 h, except for EDTA and associations of sodium hypochlorite (1% and 2.5%) with EDTA and of chlorhexidine with EDTA. Lipid peroxidation at 24 h was caused by EDTA and by 2.5% sodium hypochlorite with EDTA; it was also caused at 72 h by sodium hypochlorite (1% and 2.5%) and the three associations with citric acid (P < 0.05). All groups caused DNA damage when assessed by the alkaline comet assay, at 24 h and 72 h (P < 0.05). In the GEMO assay, all groups caused dsDNA damage (P < 0.05), except for chlorhexidine with EDTA. CONCLUSION: All groups showed some level of toxicity. Amongst the main solutions, chlorhexidine presented less cytotoxic potential. EDTA was the least cytotoxic of the auxiliary irrigant solutions, and the association of these two solutions showed the lowest toxicity potential amongst all groups.

Hypercholesterolemia and Ecto-enzymes of Purinergic System: Effects of Paullinia cupana.

Hypercholesterolemia is a metabolic disorder characterized by high levels of low-density lipoprotein and blood cholesterol, causing inflammatory lesion. Purinergic signaling modulates the inflammatory and immune responses through adenine nucleotides and nucleoside. Guaraná has hypocholesterolemic and antiinflammatory properties. Considering that there are few studies demonstrating the effects of guaraná powder on the metabolism of adenine nucleotides, we investigated its effects on the activity of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase activity in lymphocytes of rats with diet-induced hypercholesterolemia. The rats were divided into hypercholesterolemic and normal diet groups. Each group was subdivided by treatment: saline, guaraná powder 12.5, 25, or 50 mg/kg/day and caffeine concentration equivalent to highest dose of guaraná, fed orally for 30 days. An increase in adenosine triphosphate hydrolysis was observed in the lymphocytes of rats with hypercholesterolemia and treated with 25 or 50 mg/kg/day when compared with the other groups. The hypercholesterolemic group treated with the highest concentration of guaraná powder showed decreased ecto-adenosine deaminase activity compared with the normal diet groups. Guaraná was able to reduce the total cholesterol and low-density lipoprotein cholesterol to basal levels in hypercholesterolemic rats. High concentrations of guaraná associated with a hypercholesterolemic diet are likely to have contributed to the reduction of the inflammatory process.

Induction of cytotoxicity, oxidative stress and genotoxicity by root filling pastes used in primary teeth.

AIM: To evaluate the cytotoxicity, oxidative stress and genotoxicity in vitro of four iodoform pastes and three calcium hydroxide pastes. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) and pure calf thymus DNA (dsDNA) were exposed to extracts of the pastes. Cytotoxicity was assessed with the MTT assay. Generation of reactive oxygen species (ROS) was evaluated using a DCFH-DA assay, and lipid peroxidation was evaluated using a TBARS assay. Genotoxicity was evaluated using the alkaline comet assay and Genomodifier capacity assay (GEMO). All tests were performed after 24 h and 72 h of cell exposure, except GEMO. After performing the Kolmogorov-Smirnov test, data were analysed by Kruskal-Wallis and Dunn's post-tests, and anova with Dunnett's post-test, with a significance level established at P < 0.05. RESULTS: The MTT assay revealed that chlorhexidine, Maxitrol and neomycin sulphate + bacitracin pastes decreased cell viability after 24 h (P < 0.05). No group was associated with a significant decreased cell viability or lipid peroxidation after 72 h. Calcium hydroxide pastes increased the cell viability levels at both experimental times (P < 0.05). Lipid peroxidation was observed with the exposure of cells to calcium hydroxide pastes after 24 h (P < 0.05). Exposure to chlorhexidine, Guedes-Pinto and calcium hydroxide pastes resulted in a significant increase in ROS after 24 h (P < 0.05), whereas iodoform pastes and Calen thickened with zinc oxide significantly increased the ROS after 72 h (P < 0.05). The comet assay revealed that exposure of the PBMCs to iodoform pastes did not damage DNA at either period of time (P > 0.05). However, chlorhexidine paste caused DNA damage in dsDNA (P < 0.05). Calcium hydroxide pastes caused DNA damage in both tests (P < 0.05). CONCLUSION: The pastes varied in their ability to induce cytotoxicity, genotoxicity and oxidative stress. In general, Guedes-Pinto, Maxitrol and neomycin sulphate + bacitracin pastes exhibited better biocompatibility in vitro.

Avaliações clínica, ecográfica e anatomofisiológica do alotransplante parcial de vesícula urinária com células-tronco mesenquimais alogênicas derivadas do tecido adiposo em coelhos / Clinical, sonographic, anatomic and physiological assessments of partial allotransplant urinary bladder with allogeneic mesenchymal stem cells derived from adipose tissue in rabbits

Os problemas relacionados ao armazenamento vesical são muitos e relevantes. Eles, além de influírem de forma efetiva na qualidade de vida, podem eventualmente evoluir para falência renal. Existem vários trabalhos, os quais descrevem as propriedades imunomoduladoras e imunossupressoras das células-tronco mesenquimais derivadas do tecido adiposo (ADSCs). Objetiva-se com o presente avaliar clínica, ecográfica e anatomofisiologicamente o alotransplante parcial de bexiga a fresco em coelhos, utilizando como agente imunomodulador ADSCs alogênicas. Para isso foram utilizados 25 coelhos, sendo um deles macho e doador das ADSCs, e os outros 24 eram fêmeas, submetidas a alotransplante parcial de bexiga, sendo tratadas com ciclosporina (GCi) ou células-tronco mesenquimais (GCe). Conclui-se que as ADSCs foram suficientes para evitar sinais clínicos e ecográficos de rejeição ao alotransplante de vesícula urinária, mantendo a estrutura anatomofisiológica vesical por até 30 dias em coelhos.

The problems related to bladder storage are many and significant. In addition to effectively impacting the quality of life, they can eventually progress to kidney failure. There are several studies which describe the immunomodulatory and immunosuppressive properties of ADSCs. The aim of this study is to clinically, through sonography, anatomically and physiologically evaluate fresh partial allograft bladder from rabbits using allogeneic ADSCs as immunomodulator agents. For such, 25 rabbits were used, one being a male ADSCs donor, and the other 24 females who underwent simultaneous partial allograft bladder, being treated with cyclosporine (GCi) or mesenchymal stem cells (GCe). It was concluded that ADSCs were sufficient to prevent clinical and ultrasound signs of allograft rejection of the urinary bladder. These bladders retained the anatomophysiological structure for 30 days in rabbits.

Responsivity to PGE2 labor induction involves concomitant differential prostaglandin E receptor gene expression in cervix and myometrium.

Prostaglandin E2 (dinoprostone) is largely used for labor induction. However, one-third of patients do not respond to treatment. One cause of this poor response may be associated with changes in regulation of prostaglandin E receptors (EP1-4). In this study, we investigated EP mRNA expression in the uterine cervix and lower uterine segment myometrium for term births. Biopsies were obtained from women with successful (responders) and failed (non-responders) dinoprostone labor induction, while women that underwent spontaneous labor were included as controls. EP1 mRNA was upregulated in the cervical tissue of women who did not respond to dinoprostone induction. In addition, in the myometrium, significantly higher levels of EP3 mRNA were observed in women treated with dinoprostone, independent of their responsiveness. Dinoprostone-responders presented 3.6-fold higher levels of EP3 mRNA expression than the spontaneous labor group. Significantly higher levels of EP3 mRNA in the myometrium of the dinoprostone-treated group indicated that dinoprostone may regulate the EP3 gene on the transcriptional level. These results highlight the relationship between EP gene expression and delivery and indicate that understanding the regulation of prostaglandin E receptors may lead to improved labor induction.

Cytoprotective and genoprotective effects of ß-glucans against aflatoxin B1-induced DNA damage in broiler chicken lymphocytes.

The polysaccharide ß-glucan presents beneficial effects on the immune system, although the mechanisms of the immunomodulatory effect remain poorly understood. The potential cytoprotective and genoprotective effects of ß-glucans were evaluated in broiler chicken lymphocytes exposed to increasing concentrations of aflatoxin B1 (AFB1) and/or ß-glucans. AFB1 significantly decreased cell viability at the concentrations of 10 and 20 µg/ml at 72 h of incubation (p<0.01 and p<0.001, respectively). Moreover, the AFB1 concentrations of 1, 10 and 20 µg/ml increased DNA fragmentation levels at 24 h (p<0.001). Conversely, lymphocyte death was prevented by ß-glucans at the concentrations of 1% and 10%, indicating a cytoprotective effect. Reactive oxygen species levels were increased in the cells treated with 20 µg/ml AFB1 at 24 h (p<0.05) and 10% ß-glucans with or without AFB1 at 24, 48 and 72 h of incubation (p<0.001). DNA damage increased by more than 100% in AFB1-treated lymphocytes when compared to control group. ß-glucans at 1% was able to fully revert the AFB1-induced lymphocyte DNA damage, indicating a genoprotective effect and maintaining DNA integrity. In conclusion, ß-glucans showed in vitro dose-dependent cytoprotective and genoprotective effects in broiler chicken lymphocytes exposed to AFB1.

Association between advanced oxidation protein products and 5-year mortality risk among amazon riparian elderly population.

Proteins are important targets of several modifications caused by oxidative stress, leading to structural changes and consequently partial or total loss of their functions. The oxidized proteins include advanced oxidation protein products (AOPP) derived from oxidation-modified albumin, as well as fibrinogen and lipoproteins. An increase in AOPP levels indicates an oxidative stress state and the presence of coexisting inflammation. Several investigations have also suggested an association between high AOPP levels and aging-related diseases. However, the link between elevated AOPP levels and elderly mortality risk has not yet been investigated. Here, we report on a 5-year longitudinal study that investigated the potential association between AOPP levels and mortality using a population-based representative sample of riparian elders living in Brazilian Amazon region (Maués-AM). Age, sex, socioeconomic and cultural conditions, chronic morbidities, polypharmacy, and previous morbidities were also tested as potential confounders. The AOPP levels were measured in 540 (84.78%) individuals, all of whom were followed over a 5-year period in order to establish the mortality rate. Within this study period, 74 (13.7%) elders died and 466 (86.3%) survived. The AOPP levels were higher among the elders who died within the 5-year period (46.27 ± 40.6 mmol/L) compared with those who survived (36.79 ± 20.84 mmol/L) (p = 0.002). The analysis confirmed the link between high AOPP levels and mortality risk, independent of other intervenient factors. These results suggest that elevated AOPP levels could be used to predict mortality risk in elderly patients.

In vitro effects of Ala16Val manganese superoxide dismutase gene polymorphism on human white blood cells exposed to methylmercury.

Environmental contamination by methylmercury (MeHg) is an enormous public health problem in world regions such as Amazonia. MeHg toxic effects seem to be influenced by environmental and genetic factors. However, few studies have evaluated the genetic influences of MeHg toxicity in humans. Therefore, the aim of this study was to evaluate the genetic influence of Ala16Val manganese superoxide dismutase gene polymorphism (Ala16Val-MnSOD) on the cytotoxic effects of in vitro human leukocytes exposed to MeHg. Subjects were selected from 100 individuals aged 26.4 ± 7.3 years genotyped to Ala16Val-MnSOD polymorphism (AA = 6, VV = 6, and AV = 12) to perform in vitro testing using white blood cells (WBCs). Reactive oxygen species production was measured using 2',7'-dichlorofluorescein diacetate fluorimetric assay, and cell viability was measured using MTT assay on WBC samples from the same subjects that were both exposed and not exposed to MeHg (2.5 µM for 6 h). The results showed that AA- and VV-WBCs exposed to MeHg did not display increased reactive oxygen species levels compared to those in cells that were not exposed. However, AV-leukocytes exposed to MeHg displayed increased ROS levels. Cellular viability comparison among genotypes exposed to MeHg showed that the viability of AA-WBCs was lower than that of VV-WBC, with mean values of 3.46 ± 0.13 and 3.08 ± 0.77 (standard error), respectively (P = 0.033), whereas heterozygous cells (AV) displayed intermediate values. This difference was likely due to the higher basal H2O2 production of AA-WBCs compared to that of other genotypes. These results suggest that the Ala16Val-MnSOD polymorphism has toxicogenetic effects in human cells exposed to MeHg.

The MnSOD Ala16Val SNP: relevance to human diseases and interaction with environmental factors.

The relevance of reactive oxygen species (ROS) production relies on the dual role shown by these molecules in aerobes. ROS are known to modulate several physiological phenomena, such as immune response and cell growth and differentiation; on the other hand, uncontrolled ROS production may cause important tissue and cell damage, such as deoxyribonucleic acid oxidation, lipid peroxidation, and protein carbonylation. The manganese superoxide dismutase (MnSOD) antioxidant enzyme affords the major defense against ROS within the mitochondria, which is considered the main ROS production locus in aerobes. Structural and/or functional single nucleotide polymorphisms (SNP) within the MnSOD encoding gene may be relevant for ROS detoxification. Specifically, the MnSOD Ala16Val SNP has been shown to alter the enzyme localization and mitochondrial transportation, affecting the redox status balance. Oxidative stress may contribute to the development of type 2 diabetes, cardiovascular diseases, various inflammatory conditions, or cancer. The Ala16Val MnSOD SNP has been associated with these and other chronic diseases; however, inconsistent findings between studies have made difficult drawing definitive conclusions. Environmental factors, such as dietary antioxidant intake and exercise have been shown to affect ROS metabolism through antioxidant enzyme regulation and may contribute to explain inconsistencies in the literature. Nevertheless, whether environmental factors may be associated to the Ala16Val genotypes in human diseases still needs to be clarified.

The protective effects of guaraná extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside.

The antioxidant effects of the hydro-alcoholic guaraná extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guaraná bioactive compounds were initially determined by high-performance liquid chromatography: caffeine=12.240 mg/g, theobromine=6.733 mg/g and total catechins=4.336 mg/g. Cells were exposed to 10 µM SNP during a 6 h period because the cells exhibited >90% mortality at this concentration. Guaraná was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20 mg/mL). The guaraná antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guaraná reverted the SNP toxicity mainly at lower concentrations (<5 mg), which decreased cell mortality, lipid peroxidation, DNA damage and cell oxidative stress as well as increased the SOD levels. These results demonstrate that guaraná has an antioxidant effect on NO metabolism in situations with higher cellular NO levels.

Uncaria tomentosa for Reducing Side Effects Caused by Chemotherapy in CRC Patients: Clinical Trial.

To evaluate the effectiveness of Uncaria tomentosa in minimizing the side effects of chemotherapy and improving the antioxidant status of colorectal cancer (CRC) patients, a randomized clinical trial was conducted. Patients (43) undergoing adjuvant/palliative chemotherapy with 5-Fluorouracil/leucovorin + oxaliplatin (FOLFOX4) were split into two groups: the UT group received chemotherapy plus 300 mg of Uncaria tomentosa daily and the C group received only FOLFOX4 and served as a control. Blood samples were collected before each of the 6 cycles of chemotherapy, and hemograms, oxidative stress, enzymes antioxidants, immunologic parameters, and adverse events were analyzed. The use of 300 mg of Uncaria tomentosa daily during 6 cycles of FOLFOX4 did not change the analyzed parameters, and no toxic effects were observed.

Apolipoprotein E polymorphism in elderly Japanese-Brazilian immigrants does not explain the reduced cardiovascular risk factor incidence.

Study of immigrant populations may contribute to a better understanding of the epidemiology of diseases associated with the aging process. We examined the prevalence of cardiovascular risk factors, including apolipoprotein E (ApoE) polymorphism, in elderly subjects who were born in Japan, migrated to South Brazil and have lived in that region for over 40 years, versus a group of elderly, locally born Brazilians living in the same region. These Japanese subjects came to Brazil after World War II (1950-1960) from several Japanese cities, mainly Nagasaki, Kumamoto and Hokkaido. Among 1007 subjects genotyped for ApoE polymorphism, we selected 540 elderly subjects (>60 years old), consisting of 270 Japanese-Brazilians and 270 Brazilians of European ancestry from Rio Grande do Sul State (Gaucha population). The Japanese-Brazilian group had significantly lower prevalences of obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome than did the Gaucho population group. ApoE polymorphism frequencies were similar in the two groups. The differences in cardiovascular risk factors observed in the two populations cannot be explained by ApoE polymorphism; they could be related to conservation of Japanese lifestyle habits, such as diet.

Evaluation of the potential protective effects of ad libitum black grape juice against liver oxidative damage in whole-body acute X-irradiated rats.

AIMS: The aim of this study was to evaluate the potential protective effects of ad libitum black grape (Vitis labrusca) juice against liver oxidative damage in whole-body acute X-irradiated rats. MAIN METHODS: Animals were fed ad libitum and drank voluntarily black grape juice or placebo (isocaloric glucose and fructose solution) for 6 days before and 15 days following a 6 Gy X-irradiation from a 200 kV machine. KEY FINDINGS: Irradiated animals receiving placebo showed a significant increase in the concentration of thiobarbituric acid-reactive substances (TBARS), a marker of lipid peroxidation, as well as a significant decrease in both Cu/Zn superoxide dismutase (Cu/ZnSOD) and glutathione peroxidase (GPx) activity and reduced glutathione concentration (GSH). Black grape juice supplementation resulted in a reversal of lipid peroxidation, Cu/ZnSOD activity, and GSH concentration, towards values not significantly differing from those in non-irradiated, placebo-supplemented rats. Poly(ADP-ribose) polymerase (PARP-1) and Cu/ZnSOD changes in protein expression were observed for irradiated rats. No change in p53 expression or DNA fragmentation was found. SIGNIFICANCE: Ad libitum black grape juice intake is able to restore the liver primary antioxidant system against adverse effects due to whole-body acute X-irradiation in rats after 15 days post-irradiation. The results support using antioxidant supplements as a preventive tool against radiation-induced harm.